慢性帕金森病食蟹猴焦虑与抑郁样行为的研究

Anxiety and depression like behaviors in chronic Parkinsonism of cynomolgus monkey

目的建立慢性帕金森病(Parkinson’s disease,PD)食蟹猴动物模型,评价该模型动物的焦虑与抑郁样行为。方法食蟹猴10只[年龄(15.0±1.5)岁],其中5只为慢性帕金森模型(PD模型组)、5只为正常对照组。建立评价食蟹猴焦虑与抑郁样行为学方法,包括哄骗取食测试(apathy feeding test,AFT)、人类入侵者测试(Human Intruder Test,HIT)、新颖水果测试(Novel Fruit Test,NFT)、潜在捕食者测试(Predator Confrontation Test,PCT),比较不同刺激时两组动物行为学指标的变化。结果在AFT中,PD组两侧观察食物时长均高于正常组[左侧:0.73(0.49)s,0.50(0.28)s,P<0.01;右侧:0.75(0.60)s,0.53(0.16)s,P<0.01],PD组右侧障碍,左侧拿取食物时长显著高于正常组[0.83(0.20)s,0.57(0.14)s,P<0.01]。在HIT中,PD组运动及站立行为均高于正常组,出现了异常的攀爬、磨牙、抓挠、摇晃笼具等行为(P>0.05),而笼后时长在直视期与背对期明显低于正常组[直视期:0(64.70)s,111.27(38.94)s,P=0.033;背对期:0(25.84)s,120(114.69)s,P=0.028;H=17.397];但在PCT中,PD组的拿取率低于正常组,退缩率高于正常组(P>0.05)。结论本研究建立了多角度评价非人灵长类动物焦虑抑郁的行为学方法,证实了慢性帕金森病食蟹猴模型存在不同程度的焦虑与抑郁样行为,为临床前干预研究提供了新的方法。

Objective To establish and evaluate anxiety and depression like behaviors in MPTP-induced chronic Parkinsonism cynomolgus monkey. Methods Ten cynomolgus monkeys (15.0±1.5 years old) were divided into normal group and MPTP-induced parkinsonism group(PD group), 5 animals in each group.The behavioral methods for evaluating the anxiety and depression like behaviors in non-human primates included Apathy Feeding Test (AFT), Human Intruder Test (HIT), Novel Fruit Test (NFT) and Predator Confrontation Test (PCT). The changes in behavioral indicators between the two groups were analyzed. Results In AFT, PD group spent more time in observing food on both sides, and significantly higher than that in normal group (left: 0.73(0.49)s, 0.50(0.28)s, P<0.01;right: 0.75(0.60)s, 0.53(0.16)s, P<0.01), moreover PD group had limb disorder on the right side, and spent more time in taking food which significantly more than normal group (0.83(0.20)s, 0.57(0.14)s, P<0.01). In HIT, PD group moved and stood better than that in normal group, and occurred abnormal behaviors, such as climbed, grinded, scratched and shook cages (P>0.05), while normal group spent more time in the back of cage during Stare and Back period( Stare: 0(64.70)s, 111.27(38.94)s, P=0.033;Back: 0(25.84)s, 120(114.69)s;H=17.397). Finally, PD group had lower take-up rate and higher withdrawal rate than normal group in PCT(P>0.05). Conclusion This study establishes a multi-angle evaluation of behavioral methods for anxiety and depression in non-human primates.The analysis confirmed that chronic Parkinson's disease cynomolgus monkeys has different degrees of anxiety and depression, which provides a new method for preclinical intervention in Parkinson's disease.